Oxidative stress and mitochondrial dysfunction are the underlying events of dopaminergic neurodegeneration in homocysteine rat model of Parkinson's disease
Oxidative stress and mitochondrial dysfunction are the underlying events of dopaminergic neurodegeneration in homocysteine rat model of Parkinson's disease
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DOI：
10.1016/j.neuint.2016.10.001
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发表时间：
2016-12-01
影响因子：
4.2
通讯作者：
Borah, Anupom
中科院分区：
文献类型：
--
作者：
Bhattacharjee, Nivedita;Borah, Anupom
同型半胱氨酸（Homocysteine，Hcy）在大鼠黑质内注射可引起帕金森病行为学表现和黑质多巴胺能神经元的丢失，但其神经毒性的机制尚不清楚。在本研究中，我们集中在氧化应激的神经毒性的机制之一，在同型半胱氨酸诱导的偏侧帕金森病大鼠模型。同型半胱氨酸（1.0 μ mol在2 μ L）的单侧intrinigral输注引起的抑制线粒体复合物-I活性，纹状体多巴胺的水平下降，中脑多巴胺能神经元的损失，和运动异常。同型半胱氨酸引起的黑质纹状体途径的氧化应激，增加产生的羟基自由基，减少还原型谷胱甘肽的水平和增强抗氧化酶（超氧化物歧化酶和过氧化氢酶）的活性。我们的研究结果提供了证据，氧化应激的关键参与的机制之一，Hcy诱导的多巴胺能神经毒性的黑质纹状体通路。由于氧化应激是不同帕金森病动物模型中神经退行性变的主要机制之一，并且由于Hcy在大鼠模型中引起等同的帕金森病病理，因此本研究宣布Hcy诱导的大鼠模型为可行的帕金森病啮齿动物模型。(C)2016爱思唯尔有限公司版权所有
Homocysteine (Hcy) when injected intranigrally in rat caused parkinsonian behavioural phenotypes and loss of nigral dopaminergic neurons but the underlying mechanisms of neurotoxicity remains elusive. In the present study, we focused on oxidative stress as one of the mechanisms of neurotoxicity in Hcy-induced hemiparkinsonian rat model. Unilateral intranigral infusion of Hcy (1.0 mu mol in 2 mu l) caused inhibition of mitochondrial complex-I activity, decrease in the level of striatal dopamine, loss of midbrain dopaminergic neurons, and motor abnormalities. Hcy caused oxidative stress in the nigrostriatal pathway, with increase in generation of hydroxyl radicals, depletion in the level of reduced glutathione and enhanced activity of antioxidant enzymes (superoxide dismutase and catalase). Our results provided the evidence of critical involvement of oxidative stress as one of the mechanisms underlying Hcy-induced dopaminergic neurotoxicity in nigrostriatal pathway. As oxidative stress is one of the prime mechanisms of neurodegeneration in different animal models of Parkinson's disease, and since Hcy caused equivalent parkinsonian pathologies in rat model, the present study proclaims Hcy-induced rat model as a viable rodent model of Parkinson's disease. (C) 2016 Elsevier Ltd. All rights reserved.